title: Electrophysiological and hemodynamic effects of vernakalant and flecainide during cardiac resynchronization in dyssynchronous canine hearts.
abstract: BACKGROUND
  Patients with heart failure and left bundle branch block (LBBB) are frequently treated with biventricular pacing (BiVP). Approximately one-third of them suffer from atrial fibrillation. Pharmacological conversion of atrial fibrillation is performed with drugs that slow ventricular conduction, but the effects of these drugs on the benefit of BiVP are poorly understood.
  
  
  METHODS
  Experiments were performed in dogs with chronic LBBB, investigating the effects of Vernakalant and Flecainide (n = 6 each) on hemodynamics and electrophysiology during epicardial (EPI) and endocardial BiVP. The degree of dyssynchrony and conduction slowing was quantified using QRS width and EPI electrical mapping.
  
  
  RESULTS
  Compared with LBBB, EPI and endocardial BiVP reduced QRS duration by 7% ± 9% (P < 0.05 compared with LBBB) and 20% ± 13% (P < 0.05 compared with LBBB, P < 0.05 between modes), respectively. During BiVP, the administration of Vernakalant and Flecainide increased QRS duration by 20% ± 14% (P < 0.05 compared with predrug BiVP) and 34% ± 10% (P < 0.05 compared with predrug BiVP, P < 0.05 between drugs). left ventricular (LV) dP/dtmax decreased by 16% ± 8% (P < 0.05 compared with predrug BiVP) during Vernakalant and by 14% ± 15% (P < 0.05 compared with predrug BiVP) during Flecainide. The drugs did not affect the relative changes in QRS width and LV dP/dtmax induced by BiVP.
  
  
  CONCLUSIONS
  Vernakalant and Flecainide decrease contractility, slow myocardial conduction velocity, and increase activation time. The electrical and hemodynamic benefits of BiVP are not altered by the drugs.
authors.affiliation: Departments of *Physiology; and †Cardiothoracic Surgery, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; and ‡Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland.
authors.forename: Lars B
authors.initials: LB
authors.lastname: van Middendorp
authors.forename: Marc
authors.initials: M
authors.lastname: Strik
authors.forename: Patrick
authors.initials: P
authors.lastname: Houthuizen
authors.forename: Marion
authors.initials: M
authors.lastname: Kuiper
authors.forename: Jos G
authors.initials: JG
authors.lastname: Maessen
authors.forename: Angelo
authors.initials: A
authors.lastname: Auricchio
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002037:Bundle-Branch Block / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D058406:Cardiac Resynchronization Therapy; D004285:Dogs; D004562:Electrocardiography; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D005260:Female; D005424:Flecainide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; C524581:vernakalant; D005424:Flecainide